Elastomeric silicone polymers are widely used in the field of medicine. The most common type of silicone polymer, polydimethyl siloxane (PDMS), has generally been considered to be biologically inert when implanted in the body. However, the development of a fibrous tissue capsule around silicone implants continues to be a significant problem when this material is implanted for a long period of time. Capsule formation and subsequent capsular contracture can lead to pain, implant extrusion, erosion of surrounding tissue and ultimately implant failure.
One medical implant where this mode of failure is clearly evident is in percutaneous (through the skin) access devices. The lack of tissue bonding leads to the invasion of bacteria and subsequent infection. Earlier devices have lead to infection at the access site and the ultimate failure and removal of the implant.
The design of a percutaneous access device is one of the most challenging problems that faces the medical community today. One of the most common percutaneous devices used today is the peritoneal dialysis (PD) catheter, which consists of a catheter with fabric cuffs that is placed subcutaneous to anchor the device with scar tissue. Subcutaneous scar tissue forms early in the healing process around the cuffs and provides an anchor for the device at the exit-site. During a longer term, the epithelial tissue tunnels down around the catheter. This downgrowth provides access to bacteria and other pathogens that cause infection. These infections are the one barrier to greater use of these devices, Luzar, M. A., Perit. Dial. Int. 11, 333-340, 1991, and are caused by the lack of a tight seal around the catheter at the catheter-skin interface.
This need for improved percutaneous access has encouraged research efforts into both coating and design changes. Percutaneous implants have been tested that are anchored to either the cranium or tibia of animals, Jansen, J. A., et al., J. Mater. Sci. Mater. Med. 1, 192-197, 1990. The authors concluded that stabilization of a percutaneous implant was a requirement for a successful percutaneous passage. Realizing that there are many percutaneous access situations which can not be anchored to bone, this group tested an access device consisting of a 3 cm by 4 cm sintered titanium fiber mesh implanted subcutaneously and then attached to a Teflon percutaneous component, Jansen, J. A., et al., J. Biomed. Mater. Res. 25, 1535-1545, 1991. Fibrous tissue ingrowth of the mesh was intended to stabilize the implant, but early results with this implant showed that failure by tearing of the fiber mesh occurred in 30% of the implants.
One experimental device that has successfully reduced the amount of epidermal downgrowth in percutaneous implantation is made of sintered hydroxyapatite (HAP). HAP, Ca.sub.5 (PO.sub.4).sub.6 OH, a calcium phosphate mineral, is a major component of bone. This material has been used in medicine and dentistry for more than 20 years, Hench, L. L., J. Am. Ceram. Soc. 74, 1487-1510, 1991. A comparative study of these devices showed that the silicone devices had epidermal downgrowth that reached the bottom of the implant and a high rate of infection and extrusion of the implant after only 3 months. Devices made of HAP revealed limited epidermal downgrowth (.gtoreq.1 mm) at 7 months and a mild infection at 17 months, Aoki, H., et al., Med. Progress Tech. 12, 213-220, 1987. In an additional animal PD study, dogs survived for 432 days on PD without exit-site infection, using an HAP percutaneous-access device/catheter, Yoshiyama, N., et al., Perit. Dial. Int. 11 (Suppl 1), 297, 1991. The authors of this later study observed a "tight and sterile seal between the HAP device and skin tissue." These devices are brittle and require a silicone tube passing through their center, the junction between the tube and the device being a possible access for infection.
In 1969, Hench and colleagues discovered a certain range of glass compositions that could chemically bond to bones, Hench, L. L. et al., J. Biomed. Mater. Res. Symp. 2(1), 117-141, 1971. One such group of bioactive glasses, called Bioglass.RTM., composed of SiO.sub.2, CaO and P.sub.2 O.sub.5, is currently used in several medical applications, and is marketed under the trademark Bioglass.RTM. (a registered trademark of the University of Florida, currently licensed to USBiomaterials, Inc., Alachua, Fla.). Bioglass.RTM. is one of the few materials that does not produce a fibrous capsule when implanted in the body and certain Bioglass.RTM. compositions even develop an adherent bond to soft tissue, Wilson, J., Nolletti, D., Handbook of Bioactive Ceramics Vol. 1, CRC Press, Boca Raton, Fla., 283-302, 1990. Bioactive ceramic materials, like Bioglass.RTM., are inherently brittle and can not be used in bulk applications where a flexible material is needed. Coating medical devices with a bioactive glass will allow for improved soft tissue adhesion without formation of an intervening fibrous capsule, stop or reduce the epithelia downgrowth, and create a better seal that prevents bacterial access and infection.
Some of the earliest applications of bioactive glass coatings were on metal femoral implants. These coatings were either dip coated from molten glass or fired onto the metal with an enamel frit, Ducheyne, P., J. Biomed Mater Res 19:273-291,1985. Several references of the art relate to coating bioactive glass on various metal substrates, e.g., U.S. Pat. Nos. 5,480,438; 4,990,163; 4,613,516; 4,652,459; and 4,168,326.
Bioactive glasses have also been used as filler materials in bone cements, e.g. methacrylates and epoxies, as taught in U.S. Pat. Nos. 4,731,394 and 4,131,597. While certainly useful, application of these materials is limited because they are brittle, thermoset plastics, which do not have the elastomeric properties of silicone polymers used extensively in modern surgery. Precipitation of calcium phosphate and hydroxyapatite films on a substrate is known in the art, e.g. see U.S. Pat. Nos. 5,068,122 and 4,871,384. Experience has shown that these brittle films will not adhere to or spread evenly over, the hydrophobic silicone surface and will flake off after repeated flexure of the elastomer.
One technique to coat the entire implant is to use a pulsed laser deposition as described in U.S. Pat. No. 5,380,298 and published in Zabetakis, P.M., et al. ASAIO J. 40, M896-M899, 1994. A thin amorphous film of hydroxyapatite was applied to the surface of silicone tubing. The film measured between 0.5 to 1 microns in thickness and could be applied to a selected area. The coating was described as continuous. The coating failed insofar as it formed cracks when the tubing was bent. It is unclear how this cracked, amorphous and extremely thin coating would react in a percutaneous application. In addition, it is unclear how this coating process would effect the nature of bioactive glasses. Studies have shown that high temperature processes such as these can greatly alter the chemical and physical nature of bioactive glasses, thus reducing their effectiveness, Klein et al., An Introduction to Bioceramics, Hench, L. L., Wilson, J.
Eds. World Scientific, Singapore, 199-221,1993.
U.S. Pat. No. 5,522,896 ("the '896 patent") discloses a non-percutaneous prosthesis, reconstructive sheeting and composite material which exhibit tissue adhesion and biocompatability, moldability, trimability and flexibility. Experiment No. 7 of the '896 patent describes coating silicone adhesive onto a breast prosthesis. Greater than 200 mesh hydroxyapatite was spread onto a flat surface. The adhesive-coated surface was pressed onto the hydroxyapatite particles, and hydroxyapatite particles smaller than 300 mesh were sprinkled onto the coated surface to fill in the voids between the larger hydroxyapatite particles. The non-percutaneous prosthesis comprises a biocompatible composite material which is made of an elastomeric material and bio-active ceramic or glass particles.